The long-range objective of this project is to study interactions between various neurotransmitter systems at the morphological and molecular level. In order to accomplish these objectives a part of our study will be devoted to mapping out various monoaminergic neuronal systems in the murine and primate CNS. This will be accomplished by the immunohistochemical localization of the synthesizing enzymes and it will be corroborated with biochemical assays. Another part of our study will be concerned with the mechanisms involved in the regulation of the synthesizing enzymes and with the regulation of the monoamine synthesis itself. We will explore the physiological significance of c-AMP elicited stimulation of tyrosine hydroxylase (TH) activity, and we will characterize the kinetic and physico-chemical state of TH activated by various stimuli. We will also investigate the properties of the PNMT containing neuronal systems, and we will primarily examine the biosynthesis and disposition of epinephrine (E) in various regions of the CNS. In a separate study the effects of neuroleptics on the DA system will be investigated. Data obtained in this study will elucidate the alterations in the pre- and postsynaptic DA neuronal systems following acute and chronic administration of neuroleptics. The mechanisms underlying the reversal of apomorphine-elicited inhibition of synaptosomal TH activity by neuroleptics will be investigated. The apomorphine-elicited inhibition of synaptosomal TH activity will be used as a test for predicting antipsychotic activity of drugs and for measuring plasma neuroleptic levels in schizophrenic patients.